Center for Molecular Medicine and Colon Cancer Prevention Program, University of Connecticut Health Center, Farmington, CT 06030, USA.
Carcinogenesis. 2011 Mar;32(3):343-50. doi: 10.1093/carcin/bgq248. Epub 2010 Nov 23.
Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa that can dramatically increase the risk of colon cancers. In the present study, we evaluated the effects of a dietary intervention of freeze-dried black raspberries (BRB), a natural food product with antioxidant and anti-inflammatory bioactivities, on disease severity in an experimental mouse model of UC using 3% dextran sodium sulfate (DSS). C57BL/6J mice were fed either a control diet or a diet containing BRB (5 or 10%) for 7-14 days and then the extent of colonic injury was assessed. Dietary BRB markedly reduced DSS-induced acute injury to the colonic epithelium. This protection included better maintenance of body mass and reductions in colonic shortening and ulceration. BRB treatment, however, did not affect the levels of either plasma nitric oxide or colon malondialdehyde, biomarkers of oxidative stress that are otherwise increased by DSS-induced colonic injury. BRB treatment for up to 7 days suppressed tissue levels of several key pro-inflammatory cytokines, including tumor necrosis factor α and interleukin 1β. Further examination of the inflammatory response by western blot analysis revealed that 7 day BRB treatment reduced the levels of phospho-IκBα within the colonic tissue. Colonic cyclooxygenase 2 levels were also dramatically suppressed by BRB treatment, with a concomitant decrease in the plasma prostaglandin E₂ (276 versus 34 ng/ml). These findings demonstrate a potent anti-inflammatory effect of BRB during DSS-induced colonic injury, supporting its possible therapeutic or preventive role in the pathogenesis of UC and related neoplastic events.
溃疡性结肠炎(UC)是一种结肠黏膜的慢性炎症性疾病,可显著增加结肠癌的风险。在本研究中,我们使用 3%葡聚糖硫酸钠(DSS)评估了具有抗氧化和抗炎生物活性的天然食品黑莓冻干物(BRB)的饮食干预对 UC 实验小鼠模型疾病严重程度的影响。C57BL/6J 小鼠分别喂食对照饮食或含 BRB(5%或 10%)的饮食 7-14 天,然后评估结肠损伤程度。饮食 BRB 明显减轻了 DSS 诱导的结肠上皮急性损伤。这种保护作用包括更好地维持体重以及减少结肠缩短和溃疡。然而,BRB 治疗并未影响血浆一氧化氮或结肠丙二醛的水平,这两种生物标志物在 DSS 诱导的结肠损伤时会升高。BRB 治疗长达 7 天可抑制几种关键促炎细胞因子的组织水平,包括肿瘤坏死因子-α和白细胞介素 1β。通过 Western blot 分析进一步检查炎症反应,发现 BRB 治疗 7 天可降低结肠组织中磷酸化 IκBα的水平。BRB 治疗还显著抑制了结肠环氧化酶 2 的水平,同时血浆前列腺素 E₂(276 与 34ng/ml)下降。这些发现表明 BRB 在 DSS 诱导的结肠损伤中具有强大的抗炎作用,支持其在 UC 发病机制和相关肿瘤事件中的可能治疗或预防作用。